Relaxin-3 is a relaxin/insulin-like family peptide that is expressed predominantly in the nucleus incertus. The nucleus incertus is a stress-responsive brainstem nucleus that projects widely to forebrain regions involved in anxiety, depression, eating, addiction, central processing of pain, and cognition. The cognate receptor for relaxin-3 is RXFP3, and studies of RXFP3 function using relaxin-3 and relaxin-3-derived peptide agonists and antagonists indicate that RXFP3 is a potential target for the treatment of anxiety disorders, depression and pain, among others. Novel small molecule RXFP3 agonists and antagonists will be valuable tools to elucidate the functions of relaxin-3 and its actions at RXFP3 receptors. During the reporting period, the team established a research plan and received RXP3-expressing cell lines to begin adaptation of an assay to enable high-throughput screening.